Chung-Hung Shih

Comparisons of predictive performance of breathing pattern variability measured during T-piece, automatic tube compensation, and pressure support ventilation for weaning intensive care unit patients from mechanical ventilation.

Objective:To investigate the influence of different ventilatory supports on the predictive performance of breathing pattern variability for extubation outcomes in intensive care unit patients. Design and Setting:A prospective measurement of retrospectively analyzed breathing pattern variability in a medical center. Patients:Sixty-eight consecutive and ready-for-weaning patients were divided into success (n = 45) and failure (n = 23) groups based on their extubation outcomes. Measurements:Breath-to-breath analyses of peak inspiratory flow, total breath duration, tidal volume, and rapid shallow breathing index were performed for three 30-min periods while patients randomly received T-piece, 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure, and 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure trials. Coefficient of variations and data dispersion (standard descriptor values SD1 and SD2 of the Poincaré plot) were analyzed to serve as breathing pattern variability indices. Main Results:Under all three trials, breathing pattern variability in extubation failure patients was smaller than in extubation success patients. Compared to the T-piece trial, 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure and 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure decreased the ability of certain breathing pattern variability indices to discriminate extubation success from extubation failure. The areas under the receiver operating characteristic curve of these breathing pattern variability indices were: T-piece (0.73–0.87) > 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure (0.60–0.79) > 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure (0.53–0.76). Analysis of the classification and regression tree indicated that during the T-piece trial, a SD1 of peak inspiratory flow >3.36 L/min defined a group including all extubation success patients. Conversely, the combination of a SD1 of peak inspiratory flow ≤3.36 L/min and a coefficient of variations of rapid shallow breathing index ≤0.23 defined a group of all extubation failure patients. The decision strategies using SD1 of peak inspiratory flow and coefficient of variations of rapid shallow breathing index measured during 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure and 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure trials achieved a less clear separation of extubation failure from extubation success. Conclusions:Since 100% inspiratory automatic tube compensation with 5 cm H2O positive end-expiratory pressure and 5 cm H2O pressure support ventilation with 5 cm H2O positive end-expiratory pressure reduce the predictive performance of breathing pattern variability, breathing pattern variability measurement during the T-piece trial is the best choice for predicting extubation outcome in intensive care unit patients patients.

Monocyte chemotactic protein-1 in the migration of differentiated leukaemic cells toward alveolar epithelial cells.

All-trans retinoic acid (ATRA) can induce acute respiratory distress syndrome in patients with acute promyelocytic leukaemia (APL). The current study investigated the role of monocyte chemotactic protein (MCP)-1 in the chemotactic transmigration of ATRA-treated NB4 (ATRA-NB4) APL cells toward A549 alveolar epithelial cells. NB4 and A549 cells were separately cultured with ATRA and/or dexamethasone (DEX). ATRA-NB4 cells were then placed in an upper insert and co-incubated with A549 cells or their conditioned medium (CM) located in a lower plate to test their transmigration activity. ATRA stimulated NB4 cells to transmigrate toward the A549 cells. The secretion of MCP-1 was enhanced by ATRA treatment in both A549 and NB4 cells. The binding assay demonstrated that ATRA-NB4 cells bound MCP-1. Pre-treatment of both CM-A549 cells with antibodies against MCP-1 and of ATRA-NB4 cells with antibodies against MCP-1 receptors reduced ATRA-NB4 cell transmigration. DEX did not suppress MCP-1 secretion and transmigration in ATRA-NB4 cells, although when applied to A549 cells, MCP-1 secretion was suppressed and ATRA-NB4 cell transmigration was attenuated. Monocyte chemotactic protein-1 secreted from alveolar epithelial cells plays an important role in the cell–cell interaction involved in the chemotactic transmigration of all-trans retinoic acid-treated acute promyelocytic leukaemia cells toward alveolar epithelial cells.

CX3CL1(+) microparticles mediate the chemoattraction of alveolar macrophages toward apoptotic acute promyelocytic leukemic cells.

Background/Aims: During the resolution phase of inflammation, release of “find-me” signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs) are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4) cells. Methods/Results: Apoptotic ATRA-NB4 cells and their conditioning medium (CM) enhanced the chemoattraction of NR8383 cells as well as their phagocytosis activity in engulfing apoptotic ATRA-NB4 cells. The levels of CX3CL1(+) apo-MPs and CX3CL1 were rapidly elevated in the CM of ATRA-NB4 cell culture after induction of apoptosis. Both exogenous CX3CL1 and apo-MPs enhanced the transmigration of NR8383 cells toward apoptotic ATRA-NB4 cells. This pro-transmigratory activity was able to be partially inhibited either by blocking the CX3CR1 (CX3CL1 receptor) of NR8383 cells with its specific antibody or by blocking the surface CX3CL1 of apo-MPs with its specific antibody before incubating these apo-MPs with NR8383 cells. Conclusion: CX3CL1(+) apo-MPs released by apoptotic cells mediate the chemotactic transmigration of alveolar macrophages.

Annexin A1 mediates the anti-inflammatory effects during the granulocytic differentiation process in all-trans retinoic acid-treated acute promyelocytic leukemic cells†

Annexin A1 (AnxA1) originating from mature neutrophils and their microparticles (MPs) plays an important anti‐inflammatory role during the resolution phase of inflammation. However, the role of AnxA1 during the process of granulocytic differentiation is still unknown. All‐trans retinoic acid (ATRA) can induce acute promyelocytic leukemic (APL) cells to differentiate along the granulocytic lineage and has been used successfully in treating APL patients. In this study, we investigated whether or not AnxA1 contributed to the anti‐inflammatory properties of ATRA‐treated APL (NB4; ATRA‐NB) cells using the transmigratory and adhesive assays. We found that ATRA was able to enhance the surface expression of AnxA1 and its receptor (FPR2/ALX) and the release of AnxA1‐containing MPs from ATRA‐NB4 cells, while the expression of annexin V was not elevated on the latter cells. Further studies demonstrated that exogenous AnxA1 could inhibit ATRA‐NB4 cells in their transmigratory activity and adhesion to endothelial cells. In addition, the transmigratory activity of ATRA‐NB4 cells can be significantly enhanced by pretreatment with a FPR2/ALX neutralizing antibody, suggesting that endogenous AnxA1 may contribute to the anti‐migratory effects. Finally, ATRA‐NB4‐derived MPs could also inhibit recipient cells in their transmigratory and adhesive activities and these anti‐inflammatory effects could be inhibited by pretreatment of MPs with a specific anti‐AnxA1 antibody. Flowcytometry studies further demonstrated that FITC‐labeled AnxA1 could be transported from MPs to the membrane of recipient ATRA‐NB4 cells. We conclude that biologically active AnxA1 may play a role in the anti‐inflammatory properties of ATRA‐treated APL cells during the process of granulocytic differentiation. J. Cell. Physiol. 227: 3661–3669, 2012.

Rapid Shallow Breathing Index and Its Predictive Accuracy Measured under Five Different Ventilatory Strategies in the Same Patient Group

The rapid shallow breathing index (RSBI) is commonly used clinically for predicting the outcome of weaning from mechanical ventilation. We compared the RSBI and its predictive accuracies measured under 5 ventilatory strategies before weaning trials. Ninety-eight patients were included and divided into successful (n=71) and failed (n=27) groups based on their weaning outcomes. The RSBI was randomly measured when patients spontaneously breathed 21% O2 with no ventilator support (the control strategy) or were connected to ventilator breathing with 21% or 40% O2 and 0 or 5 cm H2O of continuous positive airway pressure (CPAP). We found that the RSBI values did not exhibit significant differences among the 4 ventilator strategies, but all were higher than that of the control; this remained valid in the non-chronic obstructive pulmonary disease (COPD) subgroup, but not in the COPD subgroup. Values of the area under the receiver operating characteristic curve of the RSBI for the 5 strategies were 0.51-0.62 with no significant difference between any 2 strategies. The incidences of adverse reactions (respiratory rate > or =35 breaths/min or oxygen saturation < or =89% for > or =1 min) were relatively high for the 21% O2-0 and 5 cm H2O CPAP groups (20 patients each) and low for the 40% O(2)-5 cmH2O CPAP group (2 patients). We concluded that RSBI values increased with the use of a ventilator, but not with additional applications of 40% 02 and/or 5 cm H2O CPAP. Their accuracies for predicting weaning outcome were unaltered by any of these interventions, but the incidence of adverse reactions increased with the use of the ventilator and decreased with additional 40% O2 supplementation.

Annexin A1 mediates the anti‐adhesive effects of dexamethasone during the cell–cell interaction between the all‐trans retinoic acid‐treated acute promyelocytic leukemic cells and endothelial cells

Annexin A1 (AnxA1) is an important anti‐inflammatory mediator during granulocytic differentiation in all trans‐retinoic acid (ATRA) treated acute promyelocytic leukemic (APL) cells. Dexamethasone has been used successfully to prevent complications in ATRA‐treated APL patients, although its mechanism of action is still not clear. In the present study, we have examined the effect of dexamethasone on the modulation of AnxA1 in ATRA‐APL NB4 (ATRA‐NB4) cells, ATRA‐NB4 cells‐derived microparticles (MPs) and its role during cell–cell interaction between ATRA‐NB4 cells and endothelial cells. Our results have shown that dexamethasone can inhibit the percentage of ATRA‐NB4 cells expressing surface AnxA1 and its receptor FPR2/ALX in a time‐dependent manner based on flow cytometric analysis. However, dexamethasone treatment of ATRA‐NB4 cells has no significant effect on the level of AnxA1 mRNA, the total cellular level of AnxA1 protein or the release of AnxA1 from these cells, as determined by RT‐PCR, Western blotting, and ELISA, respectively. Further studies demonstrate that dexamethasone is able to significantly inhibit the adhesion of ATRA‐NB4 cells to endothelial cells, and this anti‐adhesive effect can be inhibited if the cells were pre‐treated with a neutralizing antibody specific for AnxA1. Finally, dexamethasone also enhances the release of AnxA1‐containing MPs from ATRA‐NB4 cells which can in turn prevent the adhesion of the ATRA‐NB4 cells to endothelial cells. We conclude that biologically active AnxA1 originating from dexamethasone‐treated ATRA‐APL cells and their MPs plays an anti‐adhesive effect and this contributes to inhibit the adhesion of ATRA‐APL cell to endothelial cells. J. Cell. Biochem. 114: 551–557, 2013.

Serial changes in plasma annexin A1 and cortisol levels in sepsis patients.

Annexin A1 (AnxA1), originally identified as a glucocorticoid-regulated protein, is an impor- tant endogenous anti-inflammatory mediator during the resolution phase of inflammation, and its cir- culating level has been rarely studied in sepsis patients. Glucocorticoid has been extensively used in treating patients with sepsis. However, it is unclear whether endogenous cortisol or exogenous glucocor- ticoid contributes to the regulation of AnxA1 levels in peripheral blood of sepsis patients. The aim of this study was to investigate: [1] serial changes over time in the plasma levels of AnxA1 and cortisol in sepsis patients; and [2] prognostic value of AnxA1 level in the survival of sepsis patients. Fifty-eight adult sepsis patients admitted to an intensive care unit (ICU) were enrolled. The plasma levels of cortisol and AnxA1 were determined by specific enzyme-link immunosorbent assay. Results show that the median daily levels of cortisol at the 1st, 3rd, 5th and 7th day after admission to ICU were signifi- cantly elevated over the cortisol level of the control subjects. However, the AnxA1 level was elevated in only thirty-three patients (56%) over the observation period. There was no significant correlation between cortisol levels and AnxA1 levels. Further analysis indicated that steroid treatment resulted in significant elevation of the cortisol level over time, but did not affect the AnxA1 level. AnxA1 levels were also not statistically different between surviving and non-surviving patients. In conclusions, the circu- lating level of AnxA1 is elevated in a subgroup of sepsis patients, and the AnxA1 level does not correlate with the cortisol level in the peripheral blood of sepsis patients.